Phase I immunotherapy in women with metastatic breast cancer with activated T cells targeted with anti-CD3 x anti-Her2/neu bispecific antibody.

3034 Background: Women with metastatic breast cancer (MBC) have limited treatment options. Nontoxic approaches to improve targeting and cytotoxicity directed at MBC are needed. Anti-CD3 activated T cells (ATC) can be expanded and retargeted (armed) with anti-CD3 x anti-Her2 bispecific antibody (HER2Bi). Preclinical studies showed that Her2Bi-armed ATC exhibit high levels of specific cytotoxicity, proliferate, and secrete cytokines/chemokines (Clin Canc Res 12:569, 2006).,In a phase I trial using ATC armed with Her2Bi, 17 MBC (31-86 yrs) patients (pts) were treated with 8 infusions (twice/week) for 4 weeks with 5, 10, 20, and 40 billion armed ATC/dose to determine the maximum tolerated or technically feasible dose. T cells from leukopheresis were activated and expanded with anti-CD3/IL-2 for 14 days, harvested, armed with Her2Bi at 50 ng/10ATC, and cryopreserved. IL-2 (3 x 10 IU/m/daily) and GM-CSF (250 μg/m twice/week) was given beginning 3 days prior to the 1st infusion and ending 1 week after the last infusion.,The toxicities are summarized in the Table . Restaging at 1 month revealed 1 pt who developed a PR, 9 pts with SD, 5 pts with PD. Two pts were not evaluable. Three of 5 with CA27-29 markers decreased their markers by 15-50%. In 4 patients with positive CEA markers, 2 reduced their CEA levels by >50% and 2 by >15-50%. In 5 pts with circulating Her2 receptors (Her2r), 2 decreased Her2r by >50% and 2 reduced their Her2 by >15-50%. The median follow-up was 14.9 mos for the HER2(3+) group and 15.7 mos for the HER2(0-2+) group. Median time to progression was 3 and 6 mos for the HER2(3+) and HER2 (0-2+) groups, respectively. In the HER2(3+) group, median overall survival was not been reached with median follow-up of 14.9 mos. The median survival for the HER2(0-2+) cohort is 21.3 mos. The median survival for all pts remains undefined.,These data suggest that infusions of armed targeted T cells can be safely infused and may improve overall survival in women with MBC. [Table: see text] [Table: see text].